KR20020076311A - Inulin Products with Improved Nutritional Properties - Google Patents

Abstract

The invention relates to novel inulin products and compositions thereof, to their manufacture and to their use for modulating the bacterial flora and the fermentation pattern of inulin in the large intestine of humans and mammals, to their use for providing improved inulin-associated nutritional effects/benefits, and to their use for the manufacture of a pharmaceutical composition for providing said effects/benefits in humans and mammals. The novel inulin products consist of a mixture of an easily fermentable inulin (EFI) component (preferably an oligofructose, an agave inulin, or a mixture thereof) and a hardly fermentable inulin (HFI) component (preferably a long-chain inulin with a (DP) ≥ 20, typically chicory inulin with a (DP) ≥ 23), in a weight ratio ranging from 10/90 to 70/30. The nutritional effects include improved mineral absorption, particularly calcium and magnesium, bone mineral density increase, reduction of bone mineral density loss, improvement of bone structure, modulation of lipid metabolism, stimulation of the immune system, and anti-cancer effects. The novel inulin products are particularly suitable for the manufacture of a composition or a medicament for preventing, for postponing and for treating osteoporosis in humans, particularly postmenopausal women.

Description

{Inulin Products with Improved Nutritional Properties}

Inulin is a fructan-type carbohydrate composed mainly of fructose units, which is found as a carbohydrate in many plants. Inulin can be produced by certain bacteria and also enzymatically produced from sucrose in vitro. Inulin is naturally occurring as a polydispersed mixture of carbohydrate molecules that consists essentially of fructosyl units, which form a chain in which these fructosyl units are linked to one another primarily or exclusively by beta (2,1) linkages. The predominantly straight-chain chain contains one or more side chains consisting essentially of fructosyl units and is linked to a fructosyl-fructosyl linkage at the branch point formed by the fructosyl-fructosyl? (2,6) Molecules may be formed. Inulin molecules of plant origin mainly contain one terminal glucosyl unit. Thus, the inulin molecule can be represented by the formula GFn or Fm, where G is a terminal glucosyl unit, F is a fructoolyl unit, and n and m are linked via a? (2,1) and / or? (2,6) Representing the number of fructool unit units connected to each other). Each of the numbers n + 1, m represents the degree of polymerization (DP) of the molecule of inulin. Inulin ( (Number) average degree of polymerization, expressed in terms of the average degree of polymerization. This means that the total number of saccharide units (G and F units) in a given inulin sample can be compared to the number of inulin molecules in a sample that does not take monosaccharide glucose (G) and fructose (F) and disaccharide sucrose (GF) It is the value corresponding to the total number divided. Average polymerization degree ( ) Is generally obtained by the method described by De Leenheer et al. (1).

While native inulin (i.e., inulin as it exists in plants) from plant sources appears as a polydispersed mixture of predominantly linear polysaccharide chains with a DP in the range of 2 to about 100, Inulin molecules of bacterial origin generally have much higher (DP) values, even up to about 115,000 (DP). The plant inulin is largely dependent on raw plant and harvesting, storage and processing conditions ( ). Natural (or standard grade) inulin is referred to herein as < RTI ID = 0.0 > ), Extracted from the plant material without treatment to reduce or increase it, purified and isolated, and generally represents the corresponding natural inulin ( ) To about one unit lower ( ).

Generally, inulin molecules having a low degree of polymerization, defined as (DP) < 10, are named as inulo-oligosaccharide (s), fructo-oligosaccharide (s) or oligofructose. (DP) < 10 linear and branched inulin are generally used interchangeably also herein. Oligofructose is also referred to herein as short chain inulin.

Inulin is generally produced from plant materials, mainly from the roots of Chicory ( Cichorium intybus ), as well as from tubers of Jerusalem artichoke ( Helianthus tuberosus ) (Flower heads) of Blue Agave plants, in which inulin can be present at concentrations up to about 20 wt% (wt% means wt%) based on fresh plant material . Inulin can be readily extracted from the plant parts and purified according to conventional techniques.

Natural inulin from Jericho artichokes, respectively, from chicory, is generally present in slightly branched chains (typically less than 2%, less than 1% each) having a DP in the range of from about 2 to about 70, 2 to about 40 Chain with branching formation). The natural (standard grade) chicory inulin is approximately 10 ), The natural (standard grade) Jerusalem artichoke inulin has an approximately 6 ( ).

The natural agar-inulin is generally present in the range of about 14 to about 17 Lt; RTI ID = 0.0 &gt; polydispersed &lt; / RTI &gt;

On an industrial scale, chicory inulin has conventionally been prepared by extracting chopped root with chopped hot water to obtain a crude inulin solution, which is then purified (by treatment with lime, followed by carbonation and filtration) and by preparation (treatment on ion- Treatment with activated carbon and filtration). The standard grade inulin is then obtained by spray drying from generally purified and prepared solutions. Optionally, the monomeric and dimeric saccharides are removed from the purified and prepared solution (for example by column chromatography separation as described in EP 0 670 850) and spray dried to yield approximately monomeric and dimeric saccharides There are about 10 standards ( ). &Lt; / RTI &gt; The optionally purified and prepared solution can be fractionated to remove monomeric and dimeric saccharides, as well as oligofructose (e. G., By directed crystallization as described in EP 0 769 026), followed by fractionated inulin It is isolated in the form of particles by spray drying. Depending on the method of manufacture, it can range from about 10 (standard grade) to about 30, and even higher Lt; RTI ID = 0.0 &gt; inulin. &Lt; / RTI &gt;

Similarly, the agave inulin can be obtained on an industrial scale by squeezing or extracting chopped flower heads or pulps from agave, followed by conventional purification, preparation and isolation of inulin by, for example, spray drying.

( ) &Gt; = 20 are referred to herein as long chain inulin, while inulin containing straight chain and branched chain inulin in the range of 10 to &lt; 20 ) Are referred to herein as heavy chain inulin.

Inulin from chicory is commercially available, for example, as RAFTILINE (R) from various grades from ORAFTI, Tienen, Belgium. A representative rating is Raftilin (TM) ST (about 10 &lt; RTI ID = 0.0 &gt; ) And at least about 20, generally from about 23 to about 25 (containing about 8% by weight total of glucose, fructose, and sucrose) ) With virtually no glucose, fructose and sucrose).

Agar-agar Inulin is, for example, Industrias Colibri Azul SA, Mexico. From Industrias Colibri Azul SA de CV) to 14-16 ( ) And an industrial grade agar-containing inulin guanidine (GAVEDIET) PR containing about 5 wt% total of glucose and fructose.

Oligofructose is described in the art including, for example, in vitro synthesis by enzymes from sucrose as described in US 5,314,810, and partial hydrolysis of inulin as described, for example, in EP 0 917 588 Can be obtained according to known techniques.

Oligofructose produced by enzymatic hydrolysis of chicory inulin is commercially available, for example, from RAOFTILOSE.RTM. From ORAFETU, Tiefenen, BELGIUM, for example all about 95% (% (DP) of about 2 to 9, typically about 2 to 7 (DP), of about 4.5 (DP), with an oligofructose content of ) L95 (liquid form) or Raphilulose (registered trademark) P95 (liquid form) containing glucose, fructose and sucrose in a total amount of about 5% (wt% based on total carbohydrate) (DP) of about 2 to 9, typically about 2 to 7 (DP), and about 3.5% (w / w), with an oligofructose content of about 85% (wt% based on total carbohydrate) ( ) And Laphthylose (R) L85, which contains glucose, fructose and sucrose in a total amount of about 15% and up to 20% (wt% based on total carbohydrate), commercially available in various grades in liquid form Can be obtained.

Unless otherwise indicated, the term inulin used herein refers to straight chain, as well as branched chain inulin, including inulin molecules having (DP) < 20, as well as inulin molecules having (DP)? 20.

In the food and feed industries, oligofructose is widely used as a low-calorie portion of sugar or a complete substitute, providing a body and mouth feel of sweetness, while at least about 10, preferably at least 20 (I) as a part or whole low calorie substitute of sugar with or without one or more high intensity sweeteners which provide a body and mouth feel, (ii) as a texture improver, and (iii) It is used as a substitute for low calorie fat. The use of inulin as a fat substitute is derived from the fact that inulin can form a particle gel with water having a stable, homogeneous creamy structure and good sensory receptivity.

(DP) ≥ 10, as well as oligofructose molecules with (DP) <10 are not hydrolyzed by human digestive enzymes. Thus, these molecules pass through the upper part of the digestive tract and the small intestine unaltered (Ellegard et al. (2)) to reach the larvae which are fermented by certain intestinal bacteria almost quantitatively (Roberfroid, (3). As a result, inulin and oligofructose provide very interesting nutritional properties.

First, inulin and oligofructose are considered to be dietary fibers. They reach the colon without alteration and thus provide carbon energy to the microbial gun in the colon. In this way, inulin and oligofructose stimulate the growth of intestinal bacteria in the large intestine, causing a bulking effect (i. E., A bacterial biomaterial) that stimulates the growth of intestinal bacteria in the large intestine and leads to an increase in the amount of feces, (Roberfide (4)).

In addition, inulin and oligofructose have been found to have a strong bifidogenic effect because they selectively stimulate the growth and metabolic activity of Bifidobacteria and Lactobacilli. In addition, the oral intake of inulin or oligofructose significantly increases the number of intestinal bifidobacteria, and at the same time, the number of undesirable or pathogenic bacteria in the colon, such as Clostridia and Escherichia, (Gibson et al. (5) and Wang (6)]. Thus, ingestion of inulin and oligofructose selectively increases the colonization of the colon by the beneficial bacterial species, typically Bifidobacterium, and inhibits growth of undesirable bacterial species, thereby greatly modifying and controlling the intestinal microflora. Leading to favorable prophylactic and therapeutic effects on enteroviral enteric diseases.

In vivo experiments with healthy volunteers showed that inulin (raftillin (R) ST) and oligofructose (raftillose (R) P95) were equally bifidogenic, whereas in vitro experiments showed that inulin ((DP ) ≥ 10) in the intestine showed about 2 times slower fermentation than oligofructose (DP <10) (Roberfried et al. (3)).

From these observations, the oligofructose almost completely fermented at the large intestine, or in the ascending, while inulin also reaches more or less to the more distal end of the large intestine, i. E. The transverse and inferior parts where inulin is fermented It is easy to conclude.

In vitro studies have shown that the agar-loaded inulin is generally fermented as easily as oligofructose. It is therefore assumed that the agar-agar inulin is also almost completely fermented in the large intestine of humans and mammals.

It is also described that oligofructose and inulin have preventive and therapeutic effects on the development and growth of certain cancers such as colon cancer (WO 98/52578) and breast cancer (EP 0 692 252).

The effect on breast cancer appears to be related to the immunomodulatory effects of the oligofructose, inulin and / or fermentation products thereof, mainly short chain fatty acids (SCFA), in particular the stimulating effect on the immune system (Namioka et al. ].

With respect to colon cancer (generally caused by lesion formation prior to carcinogenesis at the distal colon), long chain inulin, i.e., ) ≥20 inulin inhibited the growth of colon cancer and inhibited the growth of colon cancer by the addition of oligofructose (DP) <10) and standard grade chicory inulin (about 10 )) (WO 98/52578).

In addition, studies with healthy volunteers who were slightly hyperlipidemic showed that ingestion of oligofructose or inulin significantly reduced serum triglycerides and cholesterol (mainly LDL cholesterol) levels compared to placebo-controlled placebo treatments, (Brighenti et al. (9) and Jackson et al. (10)]. In addition, it has been demonstrated in mice studies that the addition of oligo- and fructose or inulin to high fat diets reduces serum cholesterol, as well as serum triglycerides, by more than 50% compared to the control group [Kok et al. (11)].

In addition, various studies have revealed positive effects of ingestion of oligofructose and inulin on bone mineral density (BMD) as well as intestinal absorption of minerals, especially calcium (Ca), magnesium (Mg) and iron . Shimura et al. (12), Levrat et al. (13), Remesy et al. (14), Taguchi et al. (15) and Scholz-Ahrens et al. ) Reported a study in rats in which increased absorption of calcium and, in some cases, other minerals, including magnesium, has been demonstrated to be the result of oral ingestion of inulin or oligofructose. Ohta et al. (17) and Baba et al. (18) hypothesized that the positive effects of non-digestible carbohydrates on Ca and Mg uptake occur in the large intestine. Until then, mineral absorption has been generally considered to occur primarily through the small intestine. Delzenne et al. (19) found that a diet supplemented with 10 wt% of inulin (Raftilin (R) ST) or Oligofructose (Raptylose (R) P95) Strong absorption increase and moderate absorption gain to iron and noted approximately the same effect on inulin (Raftilin (R) ST) compared to oligo-fructose (Raptylose (R) P95) . Brommage et al. (20) published a similar increase in Ca uptake in healthy rats fed a diet supplemented with 5 wt% of oligofructose (Raptylose (R) P95). Taguchi et al. (15) reported that oligo-fructose (2.5 wt% and 5 wt% in diet) increased mineral uptake, especially Ca and Mg uptake in ovariectomized rats, increased bone density and increased estrogen deficiency And bone loss. Using the same model, Scholz-Arlens et al. (16) found that the dose-dependent effect of oligofructose (Raptylose (R) P95) on calcium absorption and bone mineralization 10 wt%) was observed. In that study, oligofructose also significantly reduced the osteoporotic loss of osteoarthritis caused by ovarian cholecystectomy. In addition, increased BM uptake accompanied by increased Ca uptake in diet-fed rats containing 5 wt%, 10 wt% inulin (Raftilin (R) HP), respectively, Lt; / RTI &gt;

The discovery that inulin and oligofructose can positively affect mineral absorption from the diet and lead to increased BMD as it can affect absorption of minerals in bone tissue is very important for human health. In fact, the ability to block, slow, or inhibit calcium absorption in the body, increased bone mineral density, as well as reduced bone mineral density is very important in the case of groups of people with typical Western lifestyle and food patterns, This is because in these groups, there is an imbalance between mineral absorption and mineral reabsorption and excretion, especially with postmenopausal women, with increasing age. This imbalance causes a decrease in BMD and bone weakness, a notable step of which is known as osteoporosis. At the advanced stage, osteoporosis leads to frequent occurrence of bone fractures. Therefore, it is very important to reliably accumulate skeletal elements with high BMD during the growing season of children and adolescents. These skeletal elements actually survive the reduction of minerals caused by virtually any factor for a longer time and thus can delay or even avoid bone fractures due to advanced osteoporosis. In view of the above facts, in order to prevent or delay the undesirable osteoporosis-related conditions, and to slow down the postmenopausal mineralization leading to osteoporosis, ultimately leading to bone fractures, It is also most important to reduce the possible loss of mineral content. In addition, it is most important to be able to treat the condition of osteoporosis, particularly in the case of osteoporosis-related bone fractures. Ultimately, it is highly desirable to be able to stimulate and increase mineral uptake and bone formation in the event of an accidental bone fracture, for example, in children, adults and elderly people as needed.

In light of these, the announcement of increased mineral uptake in rats has received much attention from the medical community, increasing the BMD or bone tissue of humans in order to observe Ca absorption from the meal and increase Ca absorption in bone tissue Some research has been done to improve or improve. Ellegard et al. (2) reported that the mineral balance of the applicant for a fistula placement in which 15 g / day of inulin (Raftil® ST) or Oligofructose (Raftilos (R) P95) I checked. The ineluctance of inulin or oligofructose was found to alter the mineral excretion from the small intestine so that the effect of inulin and oligofructose on mineral absorption does not occur in the small intestine but necessarily in the large intestine (also referred to as the colon) Respectively. A study by Coudray et al. (22) using a healthy male adult (metabolic balance method) showed significantly increased Ca uptake due to a dietary intake of inulin 40 g per day. Van den Heuvel et al. (23) found that when ingested with 15 g / day of oligofructose (Raftilos (R) P95) in a healthy male adolescent study (double stable isotopic method) A significant increase in absorption was found.

The beneficial nutritional effects resulting from the ingestion of oligofructose and inulin are evidently the result of their fermentation in the large intestine. However, as reported by Roberfried et al. (3), the fermentation rate of inulin is much slower than that of oligofructose.

In addition, in vitro experiments with human excreta slurries (unpublished results) have shown to the inventors that long chain inulin (i.e., ) &Gt; = 20 inulin) is essentially free of oligofructose (i.e., inulin of (DP) &lt; 10).

On the one hand the improved nutritional effect of inulin, in particular long chain inulin, and on the other hand the above difficulties in the fermentation of inulin, especially long chain inulin, and the slow onset and consequently the low rate of fermentation in the colon, Limiting the use of long chain inulin to produce the greatest nutritional benefit in mammals and even impeding technical problems.

In addition, in most nutritional studies published so far, the relatively high daily intake of oligofructose or inulin, i.e., from 15 g to 40 g per day in human studies and from 2.5 wt% to 10 wt% Even 20 wt% has been used. Assuming to humans, a rat diet containing 2.5 wt% to 10 wt% of oligofructose or inulin corresponds to an amount of about 15 g to 60 g of oligofructose or inulin per day. This relatively high daily dose also constitutes an additional technical problem for the use of inulin to produce an improved beneficial nutritional effect, especially for the purpose of nutrition, because such relatively high doses For example, it can cause too much gas in the stomach, too high intestinal pressure, intestinal seizures, and even diarrhea.

Object of the invention

It is an object of the present invention to provide novel inulin products and compositions thereof which provide improved nutritional properties over inulin products known to humans, mammals and other vertebrates without imparting side effects.

Another object of the present invention is to provide novel inulin products and compositions thereof that modulate the intestinal composition of the colon in humans, mammals and other vertebrates, and control the fermentation pattern of inulin in the human, mammalian, and other vertebrates .

Yet another object of the present invention is to provide the use of the novel inulin products and compositions thereof for use in the manufacture of products and compositions for the production of improved nutritional effects, especially increased mineral absorption, in humans, mammals and other vertebrates .

The present invention relates to novel inulin products and compositions thereof, to their preparation and to their use for modifying and controlling the inulin fermentation pattern and composition of the feces in the large intestine of humans, mammals and other vertebrates, To compositions for providing such benefits / benefits to humans, mammals and other vertebrates, to consumer products, pharmaceutical compositions or uses thereof for use in the manufacture of medicaments.

Figure 1 is a graph showing the effect of EFI (oligofructose with predominantly 2 to 7 (DP)) and HFI (about 25 ) In a ratio by weight of 45/55, based on the total weight of the inulin product. The dionex chromatogram shows the inulin product according to the present invention.

In search of an improved inulin product, the present inventors have surprisingly found that, despite the above-mentioned negative implications of using inuline that can hardly be fermented, the present invention provides a solution to one or more of the above- Found a new inulin product containing inuline that can hardly ferment, such as long chain inulin.

According to one embodiment of the present invention, the inulin product of the present invention has a specific weight ratio EFI / HFI 10/90 to 70/1, such as an inulin component (EFI) which can be easily fermented and an inuline component (hereinafter referred to as HFI) 30 &lt; / RTI &gt;

Inulin (EFI), which can be easily fermented, as used herein, refers to straight chain as well as branched chain inulin type products that are completely or nearly completely fermented in the large intestine (ascending portion) of humans and mammals. Representative EFIs include short chain inulin (i.e., inulin with (DP) < 10) and agar inulin (i.e., Lt; / RTI &gt; inulin).

The short chain inulin is preferably selected from the group consisting of inulin (%) with a small amount of (DP) = 8 and (DP) = 9, preferably predominantly in the range of from 2 to 7 and preferably less than 5%, more preferably less than 3% Is wt% relative to total inulin). A preferred short chain inulin is an oligofructose obtained by enzymatic hydrolysis of chicory inulin.

Inulin (HFI), which can hardly be fermented, is used herein to denote that in the large intestine of humans and mammals, fermentation is scarcely initiated and that not only in the large intestine (transverse and / or descending) Branched chain inulin type product. Representative HFIs include long chain inulin (i.e., ) &Gt; = 20, as well as branched or inedible inulin in specific crystallographic forms or specific physical appearance forms that are not easily and significantly fermentable in the large intestine of humans and mammals.

Long chain inulin is preferably at least 23, more preferably at least 25, even more preferably at least 30 ( ) And preferably less than 5%, more preferably less than 3% (DP) = 9 and (DP) = 10 (% is wt% based on total inulin).

The preferred HFI is ( ) &Gt; = 20, preferably ( ) &Gt; = 23, more preferably ( ) Long chain inulin (termed long chain chicory inulin in this specification) from chicory of 25, and another preferred HFI is inulin of bacterial origin.

In a preferred embodiment, the inulin product of the present invention consists of a mixture of EFI / HFI 10/90 to 70/30, wherein the weight ratio EFI component of the short chain inulin and the HFI component of long chain inulin is abs. = 9 and (DP) = 10 is at most 5%, preferably at most 3%, more preferably at most 2%, most preferably at most 1% (% Is wt% based on total inulin, as determined by gas liquid chromatography (GLC) analysis according to (1)).

In another preferred embodiment, the inulin product of the present invention has an EFI / HFI weight ratio in the range of 10/90 to 70/30, a total amount of inulin with (DP) = 9 and (DP) = 10 at most 5% Is at most 3%, more preferably at most 2%, most preferably at most 1% (wt% based on total inulin, measured by GLC according to Drainer et al. (1)) , Agar inulin, preferably in the range of about 14 to about 17 ( ), An EFI component consisting of any mixture of inulin or agar-containing inulin and short chain inulin, and a mixture of HFI components of long chain inulin.

In a preferred inulin product according to the present invention, the weight ratio of said EFI / HFI is preferably 20/80 to 65/35, more preferably 35/65 to 65/35, even more preferably 40/60 to 45/35, 55, typically about 50/50.

In a more preferred embodiment, the inulin product of the present invention has a total content of inulin with an EFI / HFI weight ratio in the range of 10/90 to 70/30 and a (DP) = 9 and (DP) = 10 of at most 5% As the EFI component, which is at most 3%, more preferably at most 2%, most preferably at most 1% (wt% based on total inulin, measured by GLC) And long chain chicory inulin as an HFI component. In a highly preferred embodiment, the weight ratio of EFI / HFI in the inulin product ranges from 35/65 to 65/35, most preferably from 40/60 to 45/55.

According to a further highly preferred embodiment of the present invention, the inulin product according to the invention is an industrial grade inulin product, which has an EFI / HFI weight ratio of 10/90 to 70/30, preferably 35/65 to 65/35 , Most preferably from 40/60 to 45/55 and the total content of inulin having (DP) = 9 and (DP) = 10 is at most 5%, preferably at most 3%, more preferably at most Of industrial grade short chain inulin or agar diluted inulin as the EFI component, or any mixture thereof, and HFI &lt; RTI ID = 0.0 &gt; (1 &lt; / RTI &gt;Quot; refers to an inulin product comprising an industrial grade long chain inulin mixture as a component.

In an industrial grade inulin product according to the present invention, the weight ratio of the EFI (short chain inulin) component to the HFI (long chain inulin) component may be calculated as the actual amount of glucose present in each component Short chain inulin and actual long chain inulin. Thus, the actual amount of the inulin product of the present invention in the industrial grade inulin product corresponds to the sum of the amounts of the actual short chain inulin and the actual long chain inulin present in the EFI and HFI components.

Thus, industrial grade oligofructose can be used as an EFI component in industrial graded inulin products according to the present invention, which can even total up to 20%, preferably up to 15%, more preferably up to 10% %, Even more preferably at most 8%, most preferably at most 5% of glucose, fructose and hucose (wt% based on total carbohydrate in the oligofructose product).

In a more preferred industrial grade inulin product according to the present invention, the oligofructose component has a formula Fm of at least 43 wt%, wherein F represents fructosyl units and m ranges from 2 to 9, preferably from 2 to 7, Lt; / RTI &gt; molecule).

Representative industrial grade oligofructose suitable as an EFI component of an industrial grade inulin product according to the present invention is Raphthylose (R) L85, Raphthylose (R) L95 and Raphthylose (R) P95, These are all oligofructose grades obtained by enzymatic hydrolysis of chicory inulin. Suitable industrial grades of oligofructose can also be obtained by in vitro synthesis by enzymes from sucrose, for example by known methods according to the patent US 5,314,810. A suitable industrial graded agar-inulin is Gabriet® PR.

Suitable as the HFI component of the industrial grade inulin product of the present invention ) &Gt; 20 industrial long-chain inulin can contain up to about 45% (wt% based on total carbohydrate) of inulin molecules having 10 to 20 (DP). Perhaps the inulin molecule present (DP) &lt; 10 is calculated as part of the EFI component. Among the industrial grade long chain inulin, the content of glucose, fructose, and sucrose is generally very low, typically less than about 2% (% is wt% based on total carbohydrate).

Representative industrial grades of inulin, suitable as HFI ingredients, ) &Gt; = 20, preferably ( ) &Gt; = 23 long chain chicory inulin such as Raffilin (R) HP.

The inulin product of the present invention surprisingly provides significantly improved nutritional properties and its oral or intestinal intake is superior to inulin products known in humans, mammals and other vertebrates such as oligofructose, heavy chain inulin and long chain inulin It provides one or more nutrition benefits / benefits that are significantly improved. In addition, oral or intramuscular ingestion of the inulin product of the present invention may be carried out at a daily dosage which is generally lower than the daily dose required by the known inulin product to produce all of the aforementioned nutritional effects, Thereby providing the improved nutritional effect / benefit to other vertebrates.

Mammals are specifically dogs, cats, horses, rabbits, pigs, baby pigs and calves.

The inulin product of the present invention is useful for the rapid and considerable change and control of the composition of the intestinal microflora at the distal end as well as at the base of the large intestine of healthy, dysfunctional or diseased persons, mammals and other vertebrates Respectively.

Dysfunctional persons, mammals, and other vertebrates are referred to herein as those in which the body function is not functioning optimally, possibly leading to the onset of the disease later or leading to a higher risk of developing the disease Means a person, a mammal, and other vertebrate animals.

Without wishing to be hypothesized as such, the inventors believe that the improved nutritional benefit of the inulin product of the present invention is that the defined amount of inulin that can be easily fermented in the inulin product is the amount of in vivo in the large intestine of humans, It is possible to selectively modulate the growth and metabolic activity of gambling terriers and other beneficial bacteria to change and regulate current microorganisms to a microorganism composition that is much more favorable than current microorganisms and much less undesirable microorganisms, It is assumed that the bacteria result from the presence of the EFI component and the HFI component at the defined weight ratios defined so that the bacteria from the base of the large intestine to the end of the inulin product of this invention can be carried along with a defined amount of unfermented almost non fermentable inulin. Upon arrival at the distal end, the activated bacteria induce fermentation of HFI under the pressure of EFI deficiency (consumed by the bacteria in the large intestine), thus allowing HFI to rapidly and completely (e.g., in the transverse and descending regions) Fermentation. Thus, the inulin product of the present invention provides an HFI component which on one hand is reached with little alteration to the distal end of the most advantageous colonic bowel, and on the other hand through the EFI component of the inulin product of the invention, Fermentation of the HFI at the distal end of the large intestine can be easily initiated by the activated bacterium to proceed well to complete fermentation, which again provides one or more improved inulin-related nutritional benefits / benefits. Thus, the inulin product of the present invention has the ability to alter and / or control the fermentation pattern of inulin in the colon of human, mammalian and other vertebrate animals, particularly at the distal end of the large intestine.

In a further embodiment, the present invention relates to a process for preparing an inulin product according to the invention, comprising mixing the EFI component and the HFI component in the defined weight ratios defined above. Mixing may be effected by conventional techniques, for example by dry mixing of the ingredients, or by conventional techniques of inulin products formed subsequently optionally in wet mixing of the ingredients, for example by isolation into a dry form via spray drying . Wet mixing techniques include (a) isolation by well-known techniques such as spray drying, for example, of a formed inulin product optionally followed by mixing of components dissolved, dispersed or suspended in the liquid, (b) Optionally in the form of a solution, dispersion or suspension in liquid, which is in pure form, or preferably in the same liquid, of one of the components in the form of solutions, dispersions or suspensions in liquid form (C) mixing of the respective components followed by separate preparation of solutions, dispersions or suspensions of the respective components in liquid, and simultaneous drying of the inulin product of the present invention, which is formed by known techniques of inulin products, typically by spray drying; Technology, especially isolation by co-spray drying, and (d) powders by raiding with liquid or vapor water Followed by drying, typically in the presence of hot air, of the wet mixture in an agglomeration chamber, followed by cooling and isolation of the formed particles. The particles can then be sieved to isolate the inulin product of the present invention having a desired particle size, and particles outside the desired size can be recycled.

The inulin product of the present invention is preferably produced by simultaneous drying of both components in a defined weight ratio, preferably simultaneous spray drying, or during the spray drying step, wherein one component, And spray drying said components in the presence of hot air in a drying chamber to form co-dried particles or agglomerates. Isolation of the formed particles or agglomerates can be done conventionally.

Optionally, a mixing process, including a mixing process, typically a spray drying step, may include a conventional UHT (ultra-high temperature) process step to produce an inulin product with acceptable microbiological quality.

The liquid used in the preparation of the inulin product of the present invention should preferably not cause a significant degree of hydrolysis of the ingredients since otherwise the required specified weight ratios of the ingredients may no longer be met. The most suitable liquids are short chain inulin and agar diluted inulin, as well as water (a temperature above at least about 80 DEG C) which is a good solvent for long chain inulin.

The processing conditions of the wet mixing process should be appropriate, including the type of liquid, the pH, the temperature and the retention time of the solution, dispersion or suspension (i.e. the time of the component and / or inulin product formed) Is selected in such a way that the hydrolysis or deterioration of the formed inulin product or component does not occur at all or at least does not occur significantly.

In a further embodiment, the invention relates to a composition containing an effective amount of the inulin product of the present invention and one or more edible or pharmaceutically acceptable ingredients. Representative compositions include foods, feeds, beverages, functional foods, functional feeds, drugs and pharmaceuticals (including preventive and therapeutic compositions) and intermediates thereof.

Functional foods or feeds refer to foods or feeds containing food or feed ingredients that can provide health benefits in addition to the traditional nutrients they contain [The Institute of Medicine of the United States of America the National Academy of Sciences (USA; 1994)].

The edible or pharmaceutically acceptable ingredients are preferably selected from the group consisting of sugars (e.g., glucose, fructose, sucrose, lactose, galactose, maltose, isomaltulose), polyols (e.g., sorbitol, lactitol, Food or feed ingredients, food or feed intermediates, food or feed products, liquids, beverages, minerals, especially calcium sources, such as, for example, A pharmaceutically acceptable excipient, a therapeutically active substance, a drug, and a pharmaceutical composition containing at least one active ingredient.

An effective amount is an amount of the compound of the present invention that provides the improved nutritional effect / benefit to humans, mammals, and other vertebrates when the composition is ingested orally or intestinally, preferably at regular doses in a daily dose. Means the amount of inulin product.

Particularly advantageous and preferred compositions according to the invention are edible or pharmaceutically acceptable and bioavailable one or more mineral sources, especially calcium sources and / or magnesium sources and / or iron sources, such as dairy products and calcium, magnesium and iron Of the inulin product of the present invention in the presence of salts and complexes of the present invention.

Representatively, the bioavailable amount of the mineral in the mineral source present in the daily dose of the composition of the present invention is equal to the amount corresponding to the recommended daily dose (RDI value) for the mineral. However, the composition may also contain less or more bioavailable minerals than the recommended daily dose.

The compositions according to the invention may be prepared, for example, by conventional techniques involving mixing the inulin product of the invention with one or more edible or pharmaceutically acceptable ingredients, or alternatively by mixing the EFI component And HFI components with one or more of the abovementioned edible or pharmaceutically acceptable ingredients, optionally followed by preparing the resulting composition in the desired form by conventional techniques. The compositions of the present invention may be presented in any desired form, including solid, semi-solid, for example, cream or paste, gel, liquid, dispersion, suspension or emulsion.

The compositions may be in the form of, for example, all kinds of foods, feeds, beverages, functional foods and functional foods, such as bread, sweets and biscuits, cheese and other dairy products, chocolate, jams, puddings and other dairy desserts, By frozen dessert and ice cream; May be presented in the form of pharmaceutical compositions and medicaments, for example as powders, agglomerates, granules, tablets, coated tablets, lozenges, capsules, drinks, syrups, tubes, intramuscular, have.

In addition, the inulin product and its composition of the present invention may be in a form and / or package that can be used directly by the consumer, for example, a product or composition provided in tablet, granule or powder form packaged preferably in unit dosage form Can be in the form of consumer products.

In a further aspect, the invention relates to the use of an inulin product or composition according to the invention as food, feed, drink, consumer product, functional food, functional food, pharmaceutical preparation, drug or intermediates thereof.

In a further aspect, the present invention relates to a method for altering and controlling the composition of a microorganism within the large intestine of a healthy, dysfunctional or diseased person, mammalian and other vertebrate animals, especially the colon, and / To provide one or more improved inulin-related nutritional benefits / benefits to a healthy, dysfunctional, or diseased person, mammalian and other vertebrates, as well as to modify and control the pattern, To the use of an inulin product or composition according to the present invention for oral administration and / or intramuscular administration or daily administration of a daily dose.

In a further embodiment, the present invention relates to a method for the treatment and / or prophylaxis of diseases and conditions associated with inulin, especially in the colon, in the colon, especially in the colon, in healthy, dysfunctional or diseased persons, Food, beverage, consumer product, composition, functional food, functional food, pharmaceutical preparation, drug, or a combination thereof to provide for one or more of the improved inulin-related nutritional benefits / benefits To inulin products and compositions according to the invention for use as intermediates.

In a further embodiment, the invention relates to the use of inulin fermentation, in particular for the regulation and regulation of bacterial composition in the colon, in particular in the colon, in healthy, dysfunctional or diseased persons, mammals and other vertebrates Food, feed, beverage, consumer product, functional food, functional food, pharmaceutical preparation, drug, or intermediates thereof to provide at least one improved inulin-related nutritional effect / benefit To the use of inulin products and compositions according to the present invention for use in manufacture.

The improved inulin-related nutritional effects / benefits include, but are not limited to, the colon, more particularly the production of beneficial metabolites such as short chain fatty acids (SCFA's) and the production of bacterial biomaterials, Or a bacterial effect associated with a simultaneous decrease in the number of undesirable and / or pathogenic bacteria, particularly in the prebiotic action of the vital source and / or in the distal end of the large intestine, for example, , Which in turn is beneficial for the prevention and treatment of intestinal dysfunction, anomalies and disease.

In addition, the improved nutritional benefit / benefit also includes the modulation of lipid metabolism, the stimulation of the immune system, the reduction of the risk to cancer, and the prevention and therapeutic effects of cancer, particularly breast and colon cancer.

Additional benefits / benefits include improved absorption of body minerals, particularly calcium and magnesium, bone mineral density and bone tissue improvement, in healthy, dysfunctional, or diseased persons, mammals and other vertebrates, To prevent, delay, inhibit, or significantly reduce the bone mineral content and osteoporosis of women of postmenopausal age, especially postmenopausal women, gastritis, premature and diseased persons, particularly those suffering from osteoporosis Including the possibility of

In addition, the effect / benefit also allows for the strong skeleton formation of growing children, of growing young, of growing mammals and of other vertebrates, and of increasing the maximum bone mass of a person, In the second half, especially in postmenopausal women, bone mineral content reduction and osteoporosis can be prevented or delayed.

In addition, the inventors have surprisingly found that the effect of EFI present in the inulin product of the present invention exerts its effect on the intestinal microflora and that the amount of HFI present in the product is easily and completely fermented at the end of the large intestine Respectively. This characteristic of the inulin product of the present invention can be further improved by the inulin product of the lower daily dose compared to the daily dose of the known inulin product, which is necessary for obtaining similar effects, if possible all effects, Can be obtained. The improved nutritional benefit / benefit in humans, for example improved mineral absorption, is in fact about 4 g (g / g) of the inulin product of the present invention, which is in fact the inulin product itself (including industrial grade inulin) Which is the gram of the actual inulin product according to the present invention).

The daily dosage of the actual inulin product of the present invention suitable for producing the improved nutritional benefit / benefit in an adult is preferably from about 4 g to about 12 g / day, corresponding to from about 50 mg to about 150 mg / kg body weight per day g, more preferably about 6 g to about 10 g, typically about 8 g, and for babies and children, the daily dosage is preferably in the range of about 40 mg to about 400 mg per kg body weight per day to be. These low daily doses of the inulin product of the present invention are expected to provide a somewhat greater amount of the known inulin products required to produce similar effects / benefits, possibly all the effects / benefits (from about 15 g to about 40 g per day ) Increases the comfort of inulin ingestion, thus resulting in significant additional benefits in humans. Furthermore, as a result of this low daily intake of inulin, a person often suffers from a side effect that is associated with ingesting a rather high amount of inulin, such as over-gasification, intestinal pressure, edema, intestinal obstruction and / or diarrhea .

Although certain improved nutritional benefits / benefits of the present invention have been explicitly described herein with respect to humans and mammals, oral and / or intestinal ingestion of the inulin product of the present invention may also be useful for the treatment and / It should be noted that despite the other digestive system of the animal, it produces one or more of the above improved nutritional effects / benefits in other vertebrates. Examples of such vertebrates include fish, such as salmon and flounder; amphibia; reptile; And birds, such as ostriches and poultry, especially chickens and turkeys.

The invention is further illustrated by the following examples.

Example 1: Rat studies to evaluate the effect of inulin product ingestion according to the present invention on calcium absorption compared to oligofructose and long chain inulin

Calcium absorption was measured in four groups of Wistar male rats (group of 9 or 10 rats; age of 6 weeks; weight of 160-180 g).

- Group 1 : a control group that is provided with a standard semi-synthetic diet as recommended by the American Institute of Nutrition with an inorganic content according to AIN 1976;

Group 2 : a group receiving the standard semi-synthetic food containing an industrial grade oligofructose having a DP of 2 to 7;

- County 3 : about 25 ( A long-chain chicory inulin having an industrial grade having the amino acid sequence of the long chain chicory inulin;

Group 4 : An industrial grade oligofructose with a DP of from 2 to 7, prepared by co-spray drying, with an actual EFI / actual HFI weight ratio of 45/55, consistent with the product of Figure 1, ( ) Of long chain chicory inulin having an industrial grade having an amino acid sequence of SEQ ID NO:

After three weeks of gradual adaptation of the rats to the diet for 3 weeks, the rats were left for 4 weeks in the strain and each diet containing 10 wt% test oligofructose or inulin product (100 g food + 100 g Water). Food intake was monitored, and urine and urine were collected on the last 4 days of the 4th week to examine digestion and absorption of calcium. Calcium in the urine sample was measured by atomic absorption spectroscopy. Samples of the diet and samples of lyophilized and ground sides were baked at 500 占 폚, the ash was dissolved in nitric acid / hydrogen peroxide, and the calcium was measured by atomic absorption spectroscopy after dilution with milli-Q water.

Digestion absorption was calculated by the following formula:

- daily digestion absorption = amount ingested by oral ingestion;

-% digestion = 100 x {(amount ingested via oral ingestion) - amount ingested by oral route}

The results are provided in Table 1 below.

The data in Table 1 show that calcium uptake was not increased in all the test groups when compared to the control group, considering that urinary excretion of calcium was not different among all 4 groups, ) Were statistically significant compared to the control group.

Oral ingestion of oligofructose or inulin on intestinal absorption of calcium in rats Calcium Digestion Absorption (%) Group 1 ^** (control) Group 2 ^** (Oligofructose) Group 3 ^** (long-chain inulin) Group 4 (the inulin product of the present invention) M ± SD ^* min - max 47.9 ± 5.539.1-55.9 52.7 ± 6.044.0-63.1 54.1 ± 5.645.0-61.3 58.1 ± 7.450.1-61.2 * Mean value ± standard deviation; ** For comparison

Example 2: Human studies to compare the effect of inulin product ingestion according to the present invention on calcium absorption in young adolescent girls compared to oligofructose

Calcium absorption was measured in healthy adolescents (aged 11-14 years; mean weight 44 kg). In all cases it got ethical consent and informed consent. For the study, only individuals with 500 mg to 1400 mg of habitual calcium intake per day were selected. Patients were excluded from the study if they had a chronic gastrointestinal disorder, renal insufficiency or calcium homeostasis disorder, were taking prescription drugs, smoked, took birth control pills, or had a weight greater than 90% of their age. Subjects were studied using a randomized double-blind, cross-over design. The subjects were divided into two separate groups on an unemployed basis, and each day for 3 weeks, oligo-fructose or 2 batches of 1 g of the inulin product according to the invention and 1 recovery of the 4 g of placebo daily for 3 weeks Two bundles were provided. Between studies there was a 2-week wash-over period. Individuals received oligofructose or the inulin product and placebo of the present invention in random order and observers were unaware of the treatment allocation.

Two identical protocols were performed simultaneously. At protocol I (n = 30), the test product was an industrial grade oligofructose with a (DP) of 2 to 7. In Protocol II (n = 29), the test products were mainly industrial grade oligofructose with a DP of 2 to 7 and about 25 ( ), Which is a mixture of industrial grade long chain chicory inulin having a weight ratio of 45/55 (total weight of the actual short chain inulin and the actual long chain inulin content) of the industrial grade having a weight ratio . Both protocols provided placebo in the same manner as oligo and fructose / inulin. At the end of each 3-week adaptation period (8 g / day), calcium absorption was measured using a previously validated double-tracer stable isotope technique. Reference urine samples were also collected from the individuals. Individuals were fed a low calcium breakfast and one oligo-fructose, inulin product, or a 4 g batch of placebo and a glass of calcium-fortified orange juice supplemented with 10 mcg of ⁴⁶ calcium. Immediately after breakfast, 1.5 mg of ⁴² calcium was injected intravenously over 2 to 3 minutes. The diet contained about 400 mg of calcium as calcium-fortified orange juice, milk or yoghurt. The evening meal contained another serving form of calcium fortified orange juice, 10 mcg of calcium ⁴⁶ and one other oligofructose, inulin product or a 4 g batch of placebo. Individuals consumed about 1300 mg of calcium daily during an eight week study. Urine collection was started 48 hours after the isotope administration. Calcium absorption was measured by the cumulative rate of release of oral and intravenous isotopes in the 48 hour urine collection. The samples were purified using the oxalate precipitation method and the isotope ratios were determined by thermo-ionized magnetic sector mass spectrometry.

Obedience to the test was assessed by the number of open and unopened bundles, and any bundle that was not completely emptied was assumed not to be open. Obesity for the oligofructose and inulin products of the present invention was very good as shown by the data provided in Table 2 below.

Obedience Obedience Oligofructose ^** The inulin product of the present invention M ± SD ^* 95% ± 7 94% ± 12 * Mean value ± standard deviation; ** For comparison

Calcium results are provided in Table 3 below.

Calcium absorption in a healthy young adult girl Protocol Carbohydrates Calcium Absorption% (as M ± SD) ^* The p-value for the placebo (sucrose) Protocol I Sucrose ^** Oligofructose ^** 30.9 ± 10.031.8 ± 9.3 0.75 Protocol II sucrose ^** Inulin product of the invention 32.3 ± 9.838.2 ± 9.8 0.007 * Mean value ± standard deviation; ** For comparison

The results in Table 3 show that there was no significant difference in calcium absorption between Protocol I and Protocol II (p = 0.89) for sucrose (placebo) and also that oligofructose did not significantly alter calcium absorption. However, in the case of the inulin product according to the invention, a significant increase in calcium uptake, i. E. 31.8% to 38.2%, compared to placebo and also to the oligofructose was obtained, which means a relative increase of 20% .

In addition, the urinary calcium excretion studies showed that there was no significant difference in urinary calcium excretion between any of the study groups, as can be seen from the data provided in Table 4 below.

From the above experiments, it was found that the intake of inulin products according to the present invention as low as 8 g / day at the currently recommended calcium intake (about 1300 mg / day for adolescent girls) does not increase calcium absorption without increasing compensatory urinary calcium excretion It can be concluded that the intake of the same group of oligofructose 8 g / day under the same experimental conditions did not significantly increase calcium absorption.

Urine calcium excretion in healthy adolescent girls Protocol Carbohydrates Urinary calcium excretion mg / day (M ± SD) ^* The p-value for the placebo (sucrose) Protocol I Sucrose ^** Oligofructose ^** 71 ± 4879 ± 50 0.75 Protocol II sucrose ^** Inulin product of the invention 65 ± 5471 ± 50 0.57 * Mean value ± standard deviation; ** For comparison

Example 3: Rat studies assessing the effect of the inulin product ingestion of the present invention on the absorption of magnesium compared to oligofructose

Magnesium uptake was measured in Wistar male rats (group of 9 or 10 rats; age of 6 weeks; weight of 160-180 g).

- Group 1 : A control group that is provided with a standard semi-synthetic diet as recommended by the American Institute of Nutrition with an inorganic content according to AIN 1976;

Group 2 : a group receiving the standard semi-synthetic food containing an industrial grade oligofructose having a DP of 2 to 7;

Group 3 : An industrial grade oligofructose with a DP of 2 to 7, mainly prepared by co-spray drying, with an actual short chain inulin / actual long chain inulin weight ratio of 45/55, consistent with the product of FIG. 25 ( ) Of long chain chicory inulin having an industrial grade having an amino acid sequence of SEQ ID NO:

After three weeks of gradual adaptation of the rats to the diet for 3 weeks, the rats were left for 4 weeks in the strain and each diet containing 10 wt% test oligofructose or inulin product (100 g food + 100 g Water). Food intake was monitored, and urine and urine were collected on the last 4 days of the 4th week to evaluate digestion and absorption of magnesium. Magnesium in the urine, feces and feed samples was measured by atomic absorption spectroscopy and magnesium digestion and absorption was calculated as indicated in Example 1. The results are shown in Table 5 below.

Effect of oral ingestion of oligofructose or inulin products on intestinal absorption of magnesium in rats Magnesium digestion absorption (%) Group 1 ^** (control) Group 2 ^** (Oligofructose) Group 3 (inulin product of the present invention) M ± SD ^* min - max 48.8 ± 5.339.3-57.0 71.3 ± 4.565.0-78.6 76.7 ± 6.767.6-90.4 * Mean value ± standard deviation; ** For comparison

The data in Table 5 showed statistically significant increases in magnesium uptake in groups 2 and 3, particularly in group 3 with a relative increase in magnesium uptake of about 57% when compared to the control group, and an increase in magnesium uptake, Lt; RTI ID = 0.0 &gt; inulin &lt; / RTI &gt; product of the present invention.

Example 4: Evaluation of the effect of inulin product ingestion according to the present invention on lipid metabolism in rats compared with oligofructose and long chain inulin

The effects of oligofructose and inulin products on lipid metabolism were measured in Zucker male rats. Zucker rat has a mutation in the leptin receptor that rapidly develops adipose tissue instead of lean meat tissue and makes it an additional feature to provide hyperglycemia, insulin resistance and hepatic steatosis.

The following groups of rats (7 rats; age of 5) were involved in the study.

Group 1 : control group to receive a diet of standard feed;

Group 2 : a group receiving the diet of the standard feed containing oligofructose with a DP of 2 to 7;

- County 3 : about 25 ( A long-chain chicory inulin having the formula:

Group 4 : Oligofructose with an actual short chain inulin / actual long chain inulin weight ratio of 45/55, predominantly 2 to 7 (DP) and about 25 ( Of the long-chain chicory inulin having an inulin product according to the present invention.

After adapting to the diet for 1 week (control diet or a diet containing 5 wt% of each of the oligofructose, long chain inulin or inulin product according to the invention), the rats were fed with 10 wts of each test product for 6 weeks %, And then killed. Then, according to standard techniques, the parameters of fat tissue weight, liver weight, liver triglyceride concentration and activity of enzyme fatty acid synthetase in liver were examined.

The results are provided in Table 6 below.

Effect of oligofructose or inulin products on biometric and biochemical parameters in Zucker rats group Fat tissue weight (g) ^* Liver weight (g) ^* Liver triglyceride (mg / g) ^* Activity of hepatic fatty acid synthase (FAS mU / mg protein) ^* 1 (for comparison) ^** 5.94 + - 0.23 18.32 + - 0.40 452.44 + - 72.05 32.31 ± 1.88 2 (oligofructose) ^** 5.70 ± 0.23 17.28 + - 0.67 414.97 ± 50.12 22.4 ± 2.6 3 (long-chain inulin) ^** 6.06 ± 0.28 18.17 ± 1.32 500.66 + - 62.68 25.3 ± 2.6 4 (inulin product of the present invention) 4.99 ± 0.19 14.83 + - 0.60 286.64 ± 47.73 13.7 ± 0.52 * Mean value ± standard deviation; ** For comparison

From the data in Table 6 it can be clearly concluded that the inulin product according to the invention has the most pronounced effect on lipid metabolism as compared to the oligofructose and long chain inulin.

Example 5: Evaluation of the effect of the inulin product of the present invention on azoxymethane (AOM) induced carcinogenesis in rat colon

Carcinogenesis is generally known to be a complex, multistage process that occurs in three stages called initiation, promotion and progression. Initiation is defined as causing normal cells to undergo a genomic-level change that promotes the selective growth of cells by exposure to carcinogens, such as certain chemicals. Promoting generally involves clinical expression of the disclosed cells in association with altered morphological and / or phenotypic changes. Progression involves changes in genotypes and phenotypes associated with malignancy and metastasis.

Acute follicular adenomatous lesions (ACF) are presumptive precursor lesions from which adenomas and cancers develop from the colon. ACF formation inhibitors have been shown to reduce the incidence of colorectal tumors in experimental animals [Wargovich et al. (24)]. Based on these findings, ACF induction in animal models can be used to evaluate the potential prophylactic and therapeutic properties of the compounds against colon cancer.

Example 5 describes an experiment in which the effect of the inulin product of the present invention on the formation of AOM-induced ACF in the rat colon is compared with a known inulin product. The experiment was carried out as follows.

Relevant animals were divided into the desired number of groups after one week's refinement of the control diet and the control food based on AIN93G or the control food except the corn starch containing the evaluation product (10 wt%) Male Fisher 344 infant rats that provided experimental food. Feed and water were provided freely, weekly weight and daily feed intake were recorded. Two weeks after providing the diet, all animals received subcutaneous injections of AOM (Sigma, St. Louis, Missouri, USA) in saline at 16 mg per kg body weight at 7 and 8 weeks of age. At the end of the feeding period, which was 8 weeks after the last AOM injection, the animals were sacrificed using CO ₂ anesthesia. The colon was removed, flushed with potassium phosphate buffer, and fixed with 10% buffered formalin overnight. The colon was cut into bases and end portions of the same length, which were again cut into 2 cm long segments. After staining with 0.5% methylene blue, the segments were observed under an optical microscope for ACF or tumor and the number of follicular as well as the total number of ACF per lesion was counted.

Data were analyzed using SAS statistical programs and the averages were separated using a Tukey's Studentized Range Test.

The composition of the diet (in g / kg) is shown in Table 7.

The composition of the diet used in the experiment Fauna Calibrated control diet (g / kg) to contain ^** Corn starch Inulin products ^# Type of inulin product ^# County 1 ^* (control group) 397.5 (= control diet) 0.0 __ County 2 ^* 297.5 100.0 Raffiline (R) HP County 3 ^* 297.5 100.0 Raffiline (R) ST County 4 ^* 297.5 100.0 Raphthylose (R) P95 County 5 297.5 100.0 The inulin product of the present invention * Comparative test ** Control diet (g / kg unit): corn starch (397.5); Inulin product (0.0); Casein (85% protein) (200); Dextrinized corn starch (90-94% tetracarride) (132); A sucrose 100; Soybean oil (without additives) (70); Fibers [Solka-Floc (R), 200 FCC of FS & D, St. Louis, MO or equivalent] (50); Mineral mix (AIN 93G-MX) (35); Vitamin mix (AIN-93 VX) (10); L-cystine (3); Products obtained from ORAFITI (TM) (Belgium): Raftilin (TM) HP (about 25 ( ) Long-chain chicory inulin having the formula: Raffilin (R) ST (about 12 ), Raftilos (R) P95 (industrial graded oligofructose with 2 to 7 (DP)), the inulin product of the invention: the product of the formula An industrial grade oligofructose with a DP of from about 2 to about 7, produced by co-spray drying and having an actual short chain inulin / actual long chain inulin weight ratio of 45/55 and about 25 ( ) Long chain chicory inulin having an industrial grade.

result:

No statistically significant differences were found between weight gain and average daily feed intake among rats fed control diet and experimental diets. A small group of rats (blank control group) who received no AOM, received only saline solution and ate a control diet did not show evidence of ACF formation in the colon. The results of AOM-induced induction of ACF in rat colon are shown in Table 8 below.

Effect of Inulin on ACF Induction of Rat Colon by AOM group Number of animals ACF of donation ACF at the distal end Whole ACF County 1 ^* (control) 12 39.92 + 0.82 ^a 114.17 ± 1.57 ^a 155.42 ± 1.64 ^a Group 2 ^* (Raftilin (TM) HP) 10 13.30 ± 1.45 ^c 70.20 ± 1.18 ^c 83.50 ± 1.67 ^c Group 3 ^* (Raftilin (TM) ST) 10 14.20 ± 0.57 ^c 93.90 ± 1.75 ^b 109.50 ± 2.15 ^b Group 4 ^* (Raphthylose (R) P95) 10 24.80 ± 1.32 ^b 92.10 ± 1.35 ^b 116.90 ± 1.24 ^b Group 5 (inulin product of the present invention) 12 14.90 ± 0.94 ^c 63.00 ± 2.05 ^d 75.90 ± 1.54 ^d abcd: The mean ± SEM in the column with different characters is significantly different (p <0.05) by the toque's stunted range test

From Table 8, it can be concluded that AOM treatment induced ACF at the distal end as well as at the donor end of the rat colon, but mainly at the distal end.

From Table 8, ACF induction by AOM at the distal end as well as at the base of the rat crystals was inhibited by various inulin products including Raftilin (R) HP, Raftilin (R) ST, Raphilus (R) But also significantly reduced by the inulin product according to the invention as shown in the following Table 9 (this reduction is provided in% compared with the control group).

Reduction of ACF induction in rat colon by diet containing inulin product group Reduction of ACF induction in rat colon by AOM by diet containing inulin product (% compared with control group) donate Terminal all County 1 ^* (control group) - - - Group 2 ^* (Raftilin (TM) HP) 66.7 38.5 46.3 Group 3 ^* (Raftilin (TM) ST) 64.4 17.8 29.5 Group 4 ^* (Raphthylose (R) P95) 37.9 19.3 24.8 Group 5 (inulin product of the present invention) 62.7 44.8 51.2 *: Comparative test

From these results it can be concluded that the inulin product according to the present invention inhibits the induction of AOM-induced ACF in rat colon in a much stronger manner than the short chain inulin, standard grade chicory inulin and long chain chicory inulin.

Thus, the inulin product of the present invention is useful in the prevention and reduction of the risk of developing cancer in humans, mammals and other vertebrates, as well as in the treatment of cancer, in particular colon cancer, much more than short chain inulin, standard grade inulin and long chain inulin It is considered to be more effective.

references

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Claims (29)

Wherein the EFI / HFI weight ratio is in the range of 10/90 to 70/30, the EFI component is a short chain inulin having no inorganic inulin and a degree of polymerization (DP) < 10 and the HFI component has a number average degree of polymerization ) ≥ 20 and the total content of inulin having (DP) = 9 and (DP) = 10 is at most 5% (wt% wt of total inulin, measured by gas liquid chromatography (GLC) %) Of an inulin (EFI) component that can be easily fermented and an inulin (HFI) component that can hardly be fermented. Wherein the EFI / HFI weight ratio is in the range of 10/90 to 70/30 and the EFI component consists of any mixture of agar-inulin or short-chain inulin with agar-aged inulin and (DP) < ) ≥ 20 and the total amount of inulin having (DP) = 9 and (DP) = 10 is at most 5% (% is wt% based on total inulin measured by GLC). A mixture of an inulin (EFI) component that can be easily fermented and an inulin (HFI) component that can hardly be fermented. The inulin product according to claim 1 or 2, wherein the total content of inulin having (DP) = 9 and (DP) = 10 is at most 2%. The inulin product according to claim 1 or 2, wherein the total content of inulin having (DP) = 9 and (DP) = 10 is at most 1%. The inulin product according to any one of claims 1 to 4, wherein the weight ratio of the EFI / HFI components is in the range of 35/65 to 65/35. The inulin product according to any one of claims 1 to 5, wherein the HFI component is long chain chicory inulin. Use according to any one of claims 1 to 6, characterized in that it contains an industrial grade of oligofructose containing up to a total of 20% of glucose, fructose and sucrose (% by wt. Based on the total carbohydrate) Inulin, or a mixture of the oligofructose and an optional mixture of the aglycone inulin with an EFI component and an industrial grade long chain inulin HFI component, wherein the weight ratio of the actual short chain inulin / actual long chain inulin contained in the industrial grade components Is an industrial grade inulin product as defined in any one of claims 1, 2 or 5. The inulin product according to claim 7, wherein the HFI component is an industrial grade long chain chicory inulin. The inulin product according to claim 7 or 8, wherein said short chain inulin is an industrial grade oligofructose containing up to a total of 8% of glucose, fructose and sucrose (% is wt% based on total carbohydrate). Mixing the EFI component and the HFI component of the specified weight ratio by dry mixing or wet mixing the EFI component and the HFI component of the specified weight ratio and optionally isolating the subsequently obtained inulin product in a dry form, 9. The process for producing an inulin product according to any one of claims 1 to 9, wherein the process comprises a spray drying step. A composition comprising the inulin product of any one of claims 1 to 9 and at least one edible or pharmaceutically acceptable ingredient. 12. The method of claim 11, wherein said at least one edible or pharmaceutically acceptable ingredient is selected from the group consisting of sugars, polyols, hydrogenated glucose syrups, maltodextrins, sweeteners, food ingredients, feed ingredients, food additives, feed additives, food intermediates, A composition selected from the group consisting of food products, feed products, edible liquids, beverages, bioactive minerals, pharmaceutically acceptable excipients, pharmaceutically active substances, therapeutically active substances, pharmaceutical compositions and medicaments. 13. The composition of claim 12, wherein said bioavailable mineral source comprises a calcium source and / or a magnesium source and / or an iron source. The composition according to any one of claims 11 to 13, wherein the composition is food, feed, drink, consumer product, functional food, functional food, pharmaceutical composition or drug. The inulin product according to any one of claims 1 to 9, or the EFI component and the HFI component according to any one of claims 1 to 9, 13. A method of making a composition according to any one of claims 11 to 14, which comprises mixing with one or more other ingredients as defined in any one of claims 1 to 13 and optionally followed by making the composition into the desired form. The inulin product according to any one of claims 1 to 9 or the composition according to any one of claims 11 to 13 for use as food, feed, drink, consumer product, functional food, functional food, pharmaceutical preparation or drug. Use of an inulin product according to any one of claims 1 to 9 for the manufacture of a composition, food, feed, beverage, consumer product, functional food, functional food, pharmaceutical preparation, drug or intermediates thereof, Use of a composition according to any one of claims 1-6. 18. A composition according to claim 17 for the manufacture of a composition, food, feed, drink, consumer product, functional food, functional food, pharmaceutical or medicament for altering or controlling the composition of the fungus in the large intestine or colon of a human, mammalian or other vertebrate animal For manufacturing use. 18. A composition according to claim 17 for the manufacture of a composition, food, feed, drink, consumer product, functional food, functional food, pharmaceutical composition for changing or controlling the inulin fermentation pattern in the large intestine or colon of a human, mammalian or other vertebrate animal Or for the manufacture of a medicament. 18. A composition according to claim 17 for providing improved one or more inulin related nutritional effects / benefits compared to the effects provided by known inulin products or compositions thereof in humans, mammals or other vertebrates, food, feed, Drinks, consumer products, functional foods, functional feeds, pharmaceuticals or for the manufacture of medicaments. 21. The method of claim 20, wherein the improved inulin-related nutritional benefit / benefit is selected from the group consisting of dietary fiber effects, modulation of intestinal function, vital source water action and / or bifidogenicity, And magnesium and iron absorption, bone mineral density increase, bone mineral content increase, maximum bone mass increase, bone structure improvement, bone mineral density loss decrease, bone structure loss decrease, lipid metabolism control, immune system stimulation, cancer Prevention or reduction of the risk to the colon cancer, and prevention or reduction of the risk to the breast cancer. 22. A composition according to claim 21 for improving the absorption of calcium and / or magnesium in healthy persons, food, feed, beverage, consumer product, functional food, functional food, pharmaceutical preparation or use for the manufacture of a medicament. 18. Use according to claim 17 for the preparation of a pharmaceutical or medicament for preventing or reducing the risk of bone mineral loss or osteoporosis in a person or for the treatment of osteoporosis. 24. The use according to claim 23, wherein said person is a post-menopausal woman or a transgenic person. 18. Use according to claim 17 for the preparation of a pharmaceutical or medicament for preventing cancer, reducing the risk of cancer or treating cancer. Use of an inulin product according to any one of claims 1 to 9 or a product according to any one of claims 11 to 14 for use in altering or controlling the composition of the fungus in the large intestine or in the large intestine of a human, mammalian or other vertebrate animal Use of the composition of the base. The use of the inulin product according to any one of claims 1 to 9 or of any of claims 11 to 14 for use in altering or modulating the inulin fermentation pattern in the large intestine or colon of a human, mammalian or other vertebrate animal Use of a composition according to any of the preceding claims. Use of an inulin product according to any one of claims 1 to 9 for use in providing one or more inulin related nutrition benefits / benefits improved compared to the effects provided by known inulin products in humans, mammals or other vertebrates Or a composition according to any one of claims 11 to 14. 29. The use of claim 28 wherein said improved nutritional benefit / benefit is as set forth in claim 21.